Reaction Steps
A 250-mL round-bottomed flask, equipped with a magnetic stirring bar and a thermometer was fitted with a septum and a nitrogen inlet. The apparatus was charged with 1.60 g (40.0 mmol) of a 60% dispersion of sodium hydride in mineral oil. The sodium hydride was washed with 3×20 mL of dry hexane and then suspended in 40 mL of dry N,N-dimethylformamide and cooled to 0° C. To the stirred suspension was added 4.32 mL (6.21 g, 36.3 mmol) of benzyl bromide followed by dropwise addition of 3.47 g (34.6 mmol) of ketone 2 (via cannula) dissolved in 10 mL of diethyl ether over 15 min maintaining the reaction temperature at 6° C. or less. The reaction mixture was stirred for 20 minutes at 0° C., then warmed to room temperature. After 12 hours, 10 mL of water was cautiously added and the mixture was transferred to a 250-mL separatory funnel. The aqueous phase was extracted with 3×100 mL of ethyl acetate. The organic layers were individually washed with 100 mL of brine, combined, dried over sodium sulfate, filtered, concentrated and chromatographed (6 cm×33 cm column, 9:1 hexane:dichloromethane) to afford 5.93 g (89%) of benzyl ether 3 as a clear, colorless liquid: Rf =0.20 (9:1 hexane:dichloromethane). [a]54622 -1.6° (c 2.21, CH2Cl2). IR (film): 3080m, 3070m, 3035m, 3005w, 2980s, 2960s, 2930s, 2910s, 2880s, 2860s, 2975w, 1645m, 1605w, 1495m, 1480w, 1455s, 1445m, 1415w, 1375m, 1365m, 1310w, 1255w, 1205w, 1160w, 1100s, 1040m, 995m, 915s, 745s, 695s, 605m. 1H-NMR: 7.36-7.24 (m, 5H, ArH); 5.85-5.72 (m, 1H, CH=CH2); 5.06-5.00 (m, 2H, CH=CH2); 4.51 (s, 2H, ArCH2O); 3.33 (dd, J=9.1, 6.2, 1H, one of CH2OBn); 3.28 (dd, J=9.1, 6.2, 1H, one of CH2OBn); 2.27-2.19 (m, 1H, CHCH3); 1.98-1.84 (m, 2H, CH2CH=CH2); 0.93 (d, J=6.5, 3H, CHCH3). 13C NMR: 138.7, 136.8, 128 2, 127.4, 127.3, 115.8, 75.2, 72.9, 38.0, 33.3, 16.7.
